QUORUM SENSING: CONVERSATION BETWEEN BACTERIA
Bacteria also don't like being lonely and need to know they are not alone. And often they need to talk to other bacteria and interact with them. To do so, they use a mechanism called quorum sensing.
Quorum sensing is a form of bacterial communication. It was first described over 30 years ago in bioluminescent marine bacteria, Aliivibrio (Vibrio) fisheri. Symbiotic relationship between Aliivibrio fischeri and Euprymna scolopes has been studied thoroughly and it was the key finding for understanding how bacterial communication works.
Quorum is a Latin word which means a minimum number of members of a certain assembly required to be present to make a certain decision. Quorum sensing in bacteria, ‘‘involves the regulation of expression of specific genes through the accumulation of signalling compounds that mediate intercellular communication.” This bacterial cell-to-cell signalling mechanism produces and releases chemical hormone-like signal molecules called autoinducers, that increase in concentration as a function of cell density. When an autoinducer reaches a critical threshold, the bacterial population, now considered as ‘quorate’, detect and responds to this signal by altering their gene expression. Quorum sensing can be divided into 4 steps:
· intracellular synthesis of the signal molecules,
· secretion of the molecules, either actively or passively,
· detection of the signalling molecule and its binding to an inducer and
· gene transcription activation
Quorum sensing systems:
In Gram-Negative bacteria-
Two proteins- LuxI (autoinducer synthase which produces acyl-homoserine lactone (AHL) autoinducer) and LuxR (autoinducer receptor, which is the DNA-binding transcriptional activator) control the gene expression. It is mainly used for intra-species communication.
In Gram-Positive bacteria-
Gram-Positive bacteria use modified oligopeptides as autoinducers which are detected by histidine kinase receptors. Gram+ve bacteria use two processes in quorum sensing- A two-component signal transduction system and Internalization
Interspecies Communication-
Autoinducer-2 (AI-2)- a universal autoinducer molecule released by both Gram-ve and Gram+ve bacteria that enables inter-species communication.
Quorum sensing and the periodontal pathogenesis
Periodontal disease is a multifactorial inflammatory disease which causes destruction of the periodontium and also acts as a risk factor for systemic diseases. Body interface surfaces are exposed to microbial colonization resulting in establishment of microbiota lives in harmony with the host. As teeth provide hard, non-shedding surfaces there is a development of primary colonization of bacteria leading to formation of a biofilm. 1mm of dental plaque biofilm, contains approx. 200 million bacteria. Plaque biofilm is the etiologic factor for periodontitis.
In first 24 hours, plaque mainly shows Gm+ve streptococci, which provide receptor sites for secondary colonizers such as A.actinomycetemcomitans, F.nucleatum, T.forsythia, T.denticola, and P.gingivalis which are closely associated with the development of periodontal diseases.
These micro-organisms are mostly organized in communities and accumulated on substrates known as biofilm. The creation of biofilms is regulated by quorum sensing. The increased complexity and shifts in the microbial biofilm community are the result of intra- and inter-species communication. Periodontopathogenic bacteria possess the circuit AI-2 quorum sensing, which enables inter-species communication in complex bacterial communities of the oral biofilm.
Methods for measuring quorum sensing:
· Liquid chromatography
· Colorimetric method
· Polymerase chain reaction (PCR) techniques
· Signature-tagged mutagenesis (STM)
Why there is a need for eradicating the quorum sensing process-
Biofilms are more resistant to mechanical removal and host immune responses because the matrix within them shields bacteria from innate immune defences and antibiotic treatments, Hence, a new era of therapeutics has evolved which turned into a promising potential tool for elimination of infectious diseases caused by bacteria. Thus, quorum sensing inhibitors or quorum quenching play a key role in pathogenesis of disease caused by bacteria with its influence at the genetic level leading to regulation of various factors involved in the process.
Quorum Quenching:
It is a method for inhibition of bacterial virulence àSignal jamming in dental plaque biofilms. QS Inhibitors are molecules that interrupt the pathway of communication bacteria used to regulate expression of virulence factors. These naturally occurring quorum-quenching mechanisms appear to play important roles in microbe-microbe & pathogen-host interactions.
Quorum quenchers – synthetic and naturally occurring compounds
Natural quorum sensing inhibitors- Algae, Fungi, Insects (horseradish-iberin,garlic-ajoene, turmeric-curcumin, citrus flavinoids, sponge, alkaloid oroidin, furanones, grapefruit extract, pectin, and coumarin,nutmeg, sweet basil, clove extract-eugenol,methanol Piper nigrum, etc.)
Synthetic quorum sensing inhibitors- Macrolides, RNA III- related compounds, Halogenated furanones, Homoserine lactone analogue - Antagonism of Homoserine lactone activity
Conclusion and future perspectives:
Quorum sensing regulated gene expression and intra- and inter-species communication is the key to biofilm formation which represents an ever-rising problem in healthcare, being the cause of persistent and chronic infections. Although bacterial language is not yet understood in its entirety, the importance of research in this field has been recognized. Quorum sensing inhibitors have provided evidence of alternative methods for fighting bacterial infections. Further research in this area and isolation of proper Quorum sensing inhibitors, may replace the antibiotics.
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